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G Helft

Publications and source records attributed to G Helft.

At least 37 records · Page 2Linked to original sources

[Identification of unstable coronary atherosclerotic plaques].

The mechanisms of atherogenesis are better understood and the detection of atherosclerosis has improved with the different diagnostic methods currently available. However, it is almost impossible at present to differentiate high risk, unstable or vulnerable plaques from quiescent or stable plaques of atherosclerosis. This is a crucial problem given the banality of atherosclerosis on the one hand, and, on the other hand, the serious consequences (acute coronary syndromes, cerebrovascular accidents) of thrombotic occlusion at the site of an atherosclerotic plaque. It has now been established that the composition of the plaque is more important than the degree of stenosis, a fundamental concept in the risk of plaque rupture, precipitating the cascade of reactions leading to uncontrolled thrombosis. Consequently, new imaging techniques should address the problem of analysing the composition of atheromatous plaques. Endovascular ultrasonography, fast CT, angioscopy, nuclear imaging techniques and MRI are so many promising tools. However, non-invasive techniques should be distinguished from invasive ones. In all probability, it will be the former which will turn out to be the most useful diagnostic aid in pauci or asymptomatic patients. This article reviews the different imaging techniques under evaluation for the identification of risk of plaque rupture.

Angiography↗

Noninvasive in vivo human coronary artery lumen and wall imaging using black-blood magnetic resonance imaging.

BACKGROUND: High-resolution MRI has the potential to noninvasively image the human coronary artery wall and define the degree and nature of coronary artery disease. Coronary artery imaging by MR has been limited by artifacts related to blood flow and motion and by low spatial resolution. METHODS AND RESULTS: We used a noninvasive black-blood (BB) MRI (BB-MR) method, free of motion and blood-flow artifacts, for high-resolution (down to 0.46 mm in-plane resolution and 3-mm slice thickness) imaging of the coronary artery lumen and wall. In vivo BB-MR of both normal and atherosclerotic human coronary arteries was performed in 13 subjects: 8 normal subjects and 5 patients with coronary artery disease. The average coronary wall thickness for each cross-sectional image was 0.75+/-0.17 mm (range, 0.55 to 1.0 mm) in the normal subjects. MR images of coronary arteries in patients with >/=40% stenosis as assessed by x-ray angiography showed localized wall thickness of 4.38+/-0.71 mm (range, 3.30 to 5.73 mm). The difference in maximum wall thickness between the normal subjects and patients was statistically significant (P<0.0001). CONCLUSIONS: In vivo high-spatial-resolution BB-MR provides a unique new method to noninvasively image and assess the morphological features of human coronary arteries. This may allow the identification of atherosclerotic disease before it is symptomatic. Further studies are necessary to identify the different plaque components and to assess lesions in asymptomatic patients and their outcomes.

Adult↗

Detection of coronary restenosis by exercise electrocardiography thallium-201 perfusion imaging and coronary angiography in asymptomatic patients after percutaneous transluminal coronary angioplasty.

Noninvasive detection of restenosis in patients remaining asymptomatic after percutaneous transluminal coronary angioplasty (PTCA) remains a major clinical problem. The value of exercise electrocardiography (ECG) and exercise-redistribution thallium-201 single-photon emission computed tomography (SPECT) in detecting restenosis in such patients remains uncertain. Discordances between these tests and coronary angiography is a common situation. We studied 179 consecutive patients remaining asymptomatic after successful PTCA (208 vessels), who underwent 6 +/- 2 months of exercise ECG, SPECT, and coronary angiography. We sought to assess the diagnostic value of the noninvasive tests compared with coronary angiography, and identify the determinants of discordances between the tests. Restenosis (diameter stenosis >50%) was detected in 39% of patients and in 37% of vessels. The overall sensitivity, specificity, and accuracy for exercise ECG and SPECT in detecting restenosis in individual vessels were, respectively, 53% versus 63% (p = 0.06), 59% versus 77% (p = 0.0001), and 57% versus 72% (p = 0. 0001). On multivariate analysis, positive exercise ECG was associated with higher heart rate response (p = 0.02), incomplete revascularization (p = 0.004), and angiographic restenosis (p = 0. 03), whereas positive SPECT was associated with incomplete revascularization (p = 0.02), infarct-related artery PTCA (p = 0.01), and angiographic restenosis (p = 0.0001). Accuracies of the 2 tests were not significantly different in patients with incomplete revascularization or PTCA of an infarct-related vessel. Overall, SPECT is more accurate than exercise ECG in detecting asymptomatic restenosis. Nevertheless, incomplete revascularization and PTCA of an infarct-related artery could cause reversible perfusion defects regardless of restenosis, reducing the diagnostic value of SPECT in such patients.

Angioplasty, Balloon, Coronary↗

Noninvasive in vivo magnetic resonance imaging of experimental coronary artery lesions in a porcine model.

BACKGROUND: The ability to characterize and quantify coronary artery atherosclerotic lesions accurately, reproducibly, and noninvasively may allow the stratification of risk for future acute coronary syndromes and help direct therapeutic management. MRI has been shown to accurately characterize and quantify atherosclerosis; however, because of the combination of cardiac and respiratory motion artifacts, nonlinear course, and relatively small size of the coronary arteries, these techniques have not been able to be translated to the coronary system in vivo. METHODS AND RESULTS: Coronary lesions were induced in Yorkshire albino swine (n=6) with balloon angioplasty, and 4 weeks later MRI of the coronary artery lesions was performed. High-resolution in vivo images of the coronary artery wall and lesions were obtained with a double-inversion-recovery fast-spin-echo sequence in a 1.5-T MR system. There was good agreement between measurements of vessel wall thickness and area from MR images of the coronary arteries and the matched histopathology sections (n=43). The mean difference (MRI minus histopathology +/- SD) for mean wall thickness was 0.26+/-0.18 mm, and for vessel wall area, 5.65+/-3.51 mm(2). MRI was also able to visualize intralesion hematoma (sensitivity 82%, specificity 84%). CONCLUSIONS: Using a clinical MR system, we were able to image coronary artery lesions in vivo in an experimental porcine model. Further studies are needed to assess the ability of MRI to characterize coronary atherosclerotic lesions in vivo.

Animals↗

Atrial fibrillation after coronary artery bypass surgery: a model for preoperative risk stratification.

BACKGROUND: Atrial fibrillation (AF) occurs in 20% to 40% of patients after CABG. Identification of patients vulnerable for arrhythmia will allow targeting of those most likely to benefit from prophylactic therapy. The aim of the present study was to evaluate accuracy of a prospectively defined signal-averaged P-wave duration (SAPD) cutoff and additional preoperative characteristics for the prediction of AF after CABG. METHODS AND RESULTS: Patients undergoing elective isolated CABG were recruited to the present prospective study. SAPD was recorded in all patients. Filtered signals from 3 orthogonal leads were combined in a vector analysis, and total SAPD was measured preoperatively. Postoperative in-hospital AF occurred in 92 (28.2%) of 326 patients. Patients who developed AF were older (65.9 versus 61.7 years of age; P<0.0005) and had longer SAPD (158 versus 145 ms; P<0.0005) than non-AF patients. Incidence of AF increased in patients > or =75 years of age and increased progressively throughout the range of SAPD. Stepwise logistic regression analysis of preoperative variables identified that SAPD >155 ms (odds ratio, 5.37; 95% CI, 3.10 to 9.30; P<0.0005), advanced age (odds ratio, 1. 53; 95% CI, 1.26 to 1.86 per 5-year increase in age; P<0.0005), and male sex (odds ratio, 2.88; 95% CI, 1.30 to 6.40; P<0.01) independently predicted AF. Prospectively defined SAPD >155 ms predicted AF with positive and negative predictive accuracy of 49% and 84%, respectively. CONCLUSIONS: A combination of prolonged SAPD, advanced age, and male sex identifies patients at high risk for development of AF after CABG.

Adrenergic beta-Antagonists↗

Serial in vivo MRI documents arterial remodeling in experimental atherosclerosis.

BACKGROUND: Arterial remodeling in response to atherosclerosis may be outward (positive) or inward (negative) and is an important mechanism in the clinical manifestations of atherosclerosis and restenosis after percutaneous coronary interventions. Postmortem and intravascular ultrasound studies of arterial remodeling do not allow serial and noninvasive data to be obtained. In a rabbit model of atherosclerosis, we sought to validate MRI as a new tool for documentation of arterial remodeling. METHODS AND RESULTS: Watanabe heritable hyperlipidemic rabbits underwent serial MRI at baseline and 6 months after aortic balloon denudation. The lumen area had a small but significant (P=0.006) increase, from 4.36+/-0.16 to 4. 89+/-0.12 mm(2). There was a large, significant (P<0.0001) increase in the outer wall area, from 7.96+/-0.19 to 10.46+/-0.19 mm(2). The vessel wall area (a marker of atherosclerotic burden) increased significantly (P<0.0001), from 3.61+/-0.07 to 5.57+/-0.09 mm(2). Thus, the increase in atherosclerotic burden over time was completely accounted for by positive arterial remodeling. The subgroup used for histopathological validation confirmed a significant (P<0.0001) agreement between histopathology and MRI for assessment of all 3 parameters. CONCLUSIONS: MRI can provide serial and noninvasive data about the arterial wall, allowing assessment of arterial remodeling in this rabbit model. Thus, MRI appears to be a useful tool for the investigation of arterial remodeling both in native atherosclerosis and after percutaneous coronary intervention.

Animals↗

High resolution ex vivo magnetic resonance imaging of in situ coronary and aortic atherosclerotic plaque in a porcine model.

Atherosclerotic plaque composition is central to the pathogenesis of plaque disruption and acute thrombosis. Thus, there is a need for accurate imaging and characterization of atherosclerotic lesions. Even though there is no ideal animal model of atherosclerosis, the porcine model is considered to most closely resemble human atherosclerosis. We report the feasibility of MR imaging and characterizing of atherosclerotic lesions from in situ coronary arteries and aortas in an ex vivo setting and validate this with histopathology. Coronary and aortic atherosclerosis was induced in Yucatan mini-swine (n=4) by a combination of atherogenic diet (6 months) and balloon injury. All coronary arteries were imaged ex vivo on the intact heart, preserving the curvature of their course. The aorta also underwent MR imaging. The MR images were correlated with the matched histopathology sections for both the coronary arteries (n=54) and the aortas (n=43). MR imaging accurately characterized complex atherosclerotic lesions, including calcified, lipid rich, fibrocellular and hemorrhagic regions. Mean wall thickness for the coronary arteries (r=0.94, slope: 0.81) and aortas (r=0.94, slope: 0.81) as well as aortic plaque area (r=0.97, slope: 0.90) was accurately determined by MR imaging (P<0.0001). Coronary artery MR imaging is not limited by the curvature of the coronary arteries in the heart. MR imaging accurately quantifies and characterizes coronary and aortic atherosclerotic lesions, including the vessel wall, in this experimental porcine model of complex atherosclerosis. This model may be useful for future study of MR imaging of atherosclerosis in vivo.

Animals↗

The role of plaque rupture and thrombosis in coronary artery disease.

Atherosclerosis and its thrombotic complications are the major cause of morbidity and mortality in the industrialized world. The progression of atherosclerotic plaques in the coronary circulation is dependent on several risk factors. It is now clear that plaque composition is a major determinant of the risk of subsequent plaque rupture and superimposed thrombosis. The vulnerability of plaques to rupture is further determined by extrinsic triggering factors. Following rupture, the fatty core of the plaque and its high content of tissue factor provide a powerful substrate for the activation of the coagulation cascade. Plaque rupture can be clinically silent or cause symptoms of ischaemia depending on thrombus burden and the degree of vessel occlusion. In addition, plaque rupture and subsequent healing is recognized to be a major cause of further rapid plaque progression. This review looks at the mechanisms underlying the development and progression of atherosclerotic plaques, factors leading to plaque rupture and subsequent thrombosis and their clinical consequences. Finally, we speculate on targets for future research.

Animals↗

Ventricular dilation after anterior ST-elevation myocardial infarction in the thrombolytic era.

BACKGROUND: The aim of this work was to study changes in end-diastolic volume 6 months after Q-wave and non-Q-wave anterior ST-elevation myocardial infarction by echocardiography. Ventricular dilation after anterior Q-wave myocardial infarction is well-recognized. However, there is a dearth of information about the natural history of ventricular volumes after non-Q-wave myocardial infarction. METHODS: One hundred ninety patients receiving thrombolytic therapy after anterior ST-elevation myocardial infarction were studied. All patients had 2D echocardiograms and 12-lead electrocardiograms recorded within 24 hours of symptoms and at 3, 42, and 180 days later. In addition, a further electrocardiogram was recorded on day 7 to assess patients for the presence of Q waves. Peak creatine kinase over the first 3 days of admission was recorded. End-diastolic volume index was the study end point. RESULTS: Peak creatine kinase was strongly associated with ventricular dilation in both groups (P <.001). Mean end-diastolic volume in the Q-wave group increased significantly from day 1 to 6 months (P <.05) but did not alter after non-Q-wave infarction. However, when patients were selected on predefined criteria for significant change in ventricular dilation (>10 mL/m(2)), then 35% of those with and 15% of those without Q waves fell into this category. Within this group, the increase in end-diastolic volume followed a similar pattern, with the maximum percentage increase occurring between day 1 and 6 weeks. CONCLUSIONS: In the postthrombolytic group of anterior ST-elevation myocardial infarction, a minority of patients without Q-wave development also undergo significant ventricular dilation.

Adult↗

Acute antithrombotic effect of a front-loaded regimen of clopidogrel in patients with atherosclerosis on aspirin.

There is a need for a rapid antithrombotic effect after the administration of antiplatelet drugs in the setting of acute coronary syndromes and percutaneous interventions. Clopidogrel, a new thienopyridine derivative, is an efficient antiplatelet agent. However, the standard regimen of clopidogrel (75 mg/d) requires 2 to 3 days before significant antithrombotic effects. Patients with stable arterial disease on chronic aspirin therapy (n=20) were treated with clopidogrel either with a front-loaded regimen, 300 mg the first day and 75 mg/d the next 7 days, or with a standard regimen, 75 mg/d for 8 days. Blood thrombogenicity was assessed by quantification of platelet-thrombus formation in an ex vivo perfusion chamber, by ADP-induced platelet aggregation, and by ADP-induced fibrinogen binding. At 2 hours, mean total thrombus area with the standard regimen was not significantly reduced. In contrast, at 2 hours, the mean total thrombus area with the front-loaded regimen was significantly decreased by 23.1+/-8.5% versus baseline (P<0.05). ADP-induced platelet aggregation (with 5 and 10 micromol/L) was also significantly (P<0.05) reduced with the front-loaded regimen at 2 hours, with the mean platelet aggregation being 82.2+/-4.4% and 81.8+/-4.5%, respectively, versus baseline. Similarly, flow cytometry demonstrated a significant decrease (P<0. 05) in the ADP-induced fibrinogen binding (with 0.12 and 0.6 micromol/L) at 2 hours in this front-loaded regimen group (36.1+/-2. 0% and 53.2+/-9.3%). With the standard regimen, platelet activity was not significantly reduced at 2 hours. Our data suggest that a front-loaded regimen of clopidogrel added to aspirin achieves a significant antithrombotic effect at 2 hours in patients with known atherosclerotic disease on chronic aspirin therapy. This provides a rationale for using front-loaded clopidogrel in combination with aspirin in percutaneous coronary interventions.

Adenosine Diphosphate↗

In vivo dynamic real-time monitoring and quantification of platelet-thrombus formation: use of a local isotope detector.

Current methods for monitoring thrombosis and thrombus growth are invasive and provide only single-time-point data. Animal models rely mainly on flow changes as a surrogate of thrombus formation. Our aim was to validate a unique potentially noninvasive system to detect and quantify dynamic thrombus formation in vivo by using a porcine model of carotid artery injury. Thrombus growth was monitored by deposition of autologous (111)In-labeled platelet activity over the injured artery by use of miniaturized gamma detectors and Doppler blood flow. Counts were recorded at 2-minute intervals for 2 hours. The technique was validated by comparing standard antithrombotic agents against controls. Platelet recruitment was detected before significant change in flow. Thrombus formation, calculated as the area under the curve (platelets x minutes x 10(6)), was greatest for control animals (11.7+/-1.28), followed by animals treated with aspirin (6.13+/-0.91, P<0.05), heparin (2.45+/-0.34, P<0.05), and hirudin (0.2+/-0.01, P<0.01 compared with heparin). The rate of platelet deposition was assessed as the slope of the curve in the first 30 minutes (platelets x 10(6) per minute) for the following treatment groups of animals: control, 3.53+/-0.34; aspirin, 1.67+/-0. 34 (P<0.01); heparin, 1.55+/-0.3 (P<0.01); and hirudin, 0.25+/-0.03 (P<0.001). There was no statistical difference between heparin and aspirin treatments. Change in flow was assessed as reduction from baseline: control, >99+/-0.34%; aspirin, 39+/-9.1%; heparin, 36+/-12. 5%; and hirudin, 17+/-5.4%. There was no statistical difference between the aspirin- and heparin-treated groups. Morphometric analysis revealed >99+/-0.63% occlusion of the luminal area with thrombus for the control group, 43+/-14.3% for the aspirin-treated group, 30+/-5.6% for the heparin-treated group, and <10+/-1.8% for the hirudin-treated group. Assessment of platelet-thrombus formation with this technique was more sensitive than change in flow in determining antithrombotic efficacy, and thrombus formation was detected earlier. This study validates a new quantitative, sensitive, potentially noninvasive, portable, in vivo monitoring of dynamic thrombus growth, which appears applicable to phase II studies in humans.

Adenosine Diphosphate↗

Rapid oral endotracheal intubation with a fibre-optic scope in rabbits: a simple and reliable technique.

The orotracheal intubation of rabbits is complicated by their oropharyngeal anatomy. Numerous techniques to intubate rabbits have been described; however, these methods require specialized devices, tracheostomy, or are performed in a blind fashion. We describe a technique for the intubation of the rabbit under direct visualization with a standard, small-bore, fibre-optic laparoscope, which is both rapid and simple to perform.

Animals↗

[Coronary angioplasty in hemodialysis patients].

The results of balloon coronary angioplasty are very disappointing in haemodialysis patients because of the high restenosis rate. On the other hand, the use of stents in this population had not previously been assessed. This retrospective study compared 63 coronary patients on haemodialysis with a référence group of 63 paired patients with respect to gender, age, and the necessity or not of stent implantation. There was a higher frequency of hypertension (79 vs 39%) and of hypertriglyceridaema (22 vs 8%) in the haemodialysis group than in the controls. However, there was no significant difference with respect to primary success rate of angioplasty (92 and 89% respectively), nor to the development of early cardiovascular complications (4% and 1.9% respectively). After a two-year follow-up, there was no significant difference in the restenosis rate in the haemodialysis patients (33%) compared with the controls (25%). Nevertheless, the mortality rate at 2 years was higher in the dialysis group (15%) compared with the reference group (3.5%, p = 0.03). However, this mortality rate was lower than that reported in the literature in haemodialysis patients after balloon angioplasty. Therefore, haemodialysis does not increase the risk of restenosis when an optimal angiographic results is obtained either by balloon angioplasty or by angioplasty with stenting. Coronary angioplasty is a safe and effective method of revascularisation in coronary haemodialysis patients when the lesions are accessible to stenting.

Aged↗